In recent months results from a study have been released showing efavirenz plus AZT/3TC was more successful in this study than Trizivir. Controversy has surrounded the release of these study results. At the end of this article is a copy of a letter sent by a coalition of AIDS activists addressing the controversy.

Trizivir is a combination of 3 antiretroviral nucleosides in one tablet taken twice a day (AZT, 3TC, and abacavir). These 3 drugs are all from one class of therapy—nucleosides. There is no protease inhibitor or NNRTI in this regimen. Although, some doctors use Trizivir in combination with a fourth drug such as efavirenz.

Trizivir is FDA approved and there have been a number of studies in patients over the years of this therapy comparing it to other treatment regimens in order to characterize it’s utility. Trizivir is convenient, has a low number of pills to be taken, and has relatively few side effects and toxicities. This is why doctors prescribe the therapy.

Today treatment for HIV is individualized. This means that a patient can and should receive a regimen that is effective for them. Selection of such a regimen considers potency and convenience. Because we have so many FDA approved treatments today for HIV we are able to have individualization of therapy.

Recently the interim results of ACTG study 5095 reported that in this study Trizivir was less potent than efavirenz plus AZT/3TC. ACTG stands for the AIDS Clinical Trials Group, which is the NIH funded HIV/AIDS research organization. Following this recent information, Michael Weinstein, the President of the AIDS Healthcare Foundation, has conducted a public media campaign which requested that the FDA withdraw its approval for Trizivir alluding that the drug was not useful. A number of drugs for treating HIV are FDA approved and some of them are less potent than others. A decision to use a particular therapy for treatment of HIV ought to be between the patient and a knowledgable HIV care provider or doctor.

The recent PHHS HIV Treatment Guidelines list two preferred initial HIV treatments: in the PI class the Guidelines state a preference for Kaletra and in the NNRTI class they prefer efavirenz for first-line HIV therapy. The Guidelines suggest alternate therapy regimens. The alternative treatment regimens discussed by the Guidelines include other protease inhibitors, NNRTIs, and Trizivir.

The AIDS Treatment Activist Coalition (ATAC) is a national coalition of AIDS activists, many living with HIV/AIDS, working together to end the AIDS epidemic by advancing research on HIV/AIDS and broadening access to treatment. We are writing to you to express our grave concerns over your recent letter to the Food and Drug Administration asking for the withdrawal of Trizivir from the market and the advertisements on this drug that you have placed in the community press. First, we do not think the scientific data support your call for Trizivir's withdrawal. Second, your advertisements in gay papers in Los Angeles and in Washington, DC, which carry a bold red headline "Trizivir Warning" and advise in smaller black type that the drug should not be taken alone, are irresponsible and inflammatory. Further, we believe these ads are misleading and will create anxiety and confusion for people with HIV/AIDS who are now taking Trizivir and doing well, whether they are at your own clinics or in medical care elsewhere in these cities. We are also opposed to medical advice being given through press releases and advertisements, rather than by consultations between doctors and their patients.

As for the data, we would like to remind you that Trizivir did better in the A5095 study (79% VL <200 by week 32) than it did in the pivotal abacavir efficacy study which is cited in the FDA labels for abacavir and trizivir.(CNAAB3005, 60% VL <400 by week 24 and 50% by week 48). In addition, the black box warning on Trizivir's label already says "There are limited data regarding the use of this triple combination regimen [abacavir + lamivudine + zidovudine] in patients with higher viral load levels (>100,000 copies) at baseline." This supposition -- later confirmed -- was one of the reasons why the Panel on Clinical Practices for Treatment of HIV Infection convened by the Department of Health and Human Services (DHHS) and the Henry J. Kaiser Family Foundation to develop the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents in the United States did not make Trizivir a "preferred" regimen for the triple NRTI class.

Further, if you support a ban on advertising of TZV as a "sole regimen" because of an unacceptably high failure rate, where are you setting the bar? Kaletra or Sustiva + AZT+3TC may offer virologic efficacy over 90% at 48 weeks, which is why they were "preferred" by the Guidelines panel. (Indinavir and ritonavir, if tolerated, and ritonavir + saquinavir also may offer such potency.) However, many of the treatments that are now in "alternative" triple combinations -- such as atazanavir (not yet listed), amprenavir, delavirdine, nelfinavir, nevirapine, either form of saquinavir -- do not offer such potency. These therapies have ranged from 45%-80% or so in various studies. This is why they were recommended by as alternatives in the latest US Guidelines. If Trizivir is to be withdrawn from the market by FDA because of A5095's showing of a 21% failure rate by week 32, many of these other drugs would presumably have to be withdrawn as well, for their efficacy has been shown to be lower in many studies (at least in the case of the PIs, when unboosted).

Ideally, the Guidelines panel prefers to look at combinations studied for 24, 48 and 96 weeks, with % viral load below <400 and <500 copies at those time points, and CD4 count increases, in a naive population where possible, compared with a "gold standard" regimen - e.g., EFV+AZT+3TC. In the FDA approved Ziagen (abacavir) label, figures are shown from study CNAAB3003 -- ABC/AZT/3TC vs. AZT/3TC, N=173. At 16 weeks, 70% vs. 30% had a viral load
In AACTG A5095, 1,147 ARV-naive individuals were randomized to receive:

AZT + 3TC + ABC (Trizivir)

AZT + 3TC (Combivir) + Efavirenz (Sustiva)

AZT + 3TC + ABC + Efavirenz (Trizivir + Sustiva)

Virologic failure was defined as HIV RNA above 200 copies/mL at least 4 months after starting study treatment. After an average of 32 weeks on study, 167 volunteers experienced virologic failure -- 21% in the Trizivir group vs. 10% in the other two groups. Clearly Sustiva is more potent than abacavir. However, it is notable that such a high proportion of those on Trizivir alone -- 79% -- did NOT fail by week 32. This is much higher than in the pivotal studies and in the FDA label. A5095 participants on the Trizivir alone arm were offered several other options and taken off that study arm for continued follow-up. Follow-up of the other two arms will continue until September 2004. The question now will be: does Sustiva + Trizivir do better than Sustiva + Combivir.

There are many unanswered questions about how best use antiretroviral therapy and additional research is necessary to optimize care for people with HIV/AIDS in the US and elsewhere. Our advocacy must be based on a strong scientific basis, a dispassionate analysis of the data and always holding the interests of people with HIV/AIDS as our first priority. We believe AIDS Healthcare Foundation's recent actions do not meet these three criteria and hope you will reconsider your position in light of our comments.